Preliminary retrospective studies at our institution have indicated an association between viral infections and acute febrile illness, transplant rejection and mortality. However, the following have not been answered satisfactorily: 1) What is the source of the patient's virus? 2) Do viruses cause clinically relevant illness? 3) How do viral infections relate to immune function and episodes of rejection? Our objective is to answer these questions by performing an intensive prospective epidemiologic viral study. The source of virus will be sought by culturing donors, donor organs, blood products which the patients receive, and transplant staff. The relationship of viral shedding with clinical illness will be examined by prospective studies with frequent viral culturing and detailed clinical observations. Specimens will also be examined by immunofluorescence and counterelectrophoresis for evidence of viral antigens. Nonspecific and specific humoral and cell-mediated tests will be done to investigate the relationship of viral infection to immune function, and these studies will be correlated with episodes of rejection. Routine tests will include quantitation of T and B cells, a battery of viral antibody titers, mitogen stimulation using PHA and Con A, and mixed lymphocyte culture. Tests for CMV-specific cell-mediated immunity have been developed and are being evaluated prospectively as indicators or predictors of the presence and severity of CMV infections. In addition, Ara-A for treatment of CMV is being evaluated in a double-blind study.